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Biomedical subjects

I Abe

Publications and source records attributed to I Abe.

At least 253 records · Page 14Linked to original sources
PubMed1978

Phosphorylation of 1-beta-D-arabinofuranosylcytosine by the cell-free extract of rat ascites hepatoma, in relation to the mechanism of natural resistance.

The enzyme that phosphorylates 1-beta-D-arabinofuranosylcytosine (ara-C) was examined in rat ascites hepatomas to clarify whether the capacity for the phosphorylation of ara-C would be related to natural resistance of the tumors to ara-C. Ara-C kinase activity in AH-66F cells, which were moderately sensitive to ara-C, was approximately the same as that in the bone marrow of tumor-bearing rats. L-1210 leukemia, which is sensitive to ara-C, had a higher activity of the enzyme than the mouse bone marrow. On the other hand, the naturally resistant hepatomas, AH-60C, AH-109A, and AH-66, were low in their ara-C kinase activity. The enzyme activity in the cytoplasmic extract (30,000 g supernatant) of the tumor and bone marrow cells was nearly proportional to the capacity for ara-C phosphorylation in intact cells. Thus, the mechanism of natural resistance to ara-C in rat ascites hepatomas was attributed mainly to the low levels of ara-C kinase activity itself. Apparent Km of the enzyme for ara-C was about 170 micron. However, probably due to the presence of the uncompetitive type of inhibitor(s), the level of apparent Km lowered close to 40 micron at higher concentration of the protein as the source of the enzyme, showing similarity to the value in intact cells.

Animals↗
PubMed1978

Mechanism of natural resistance of rat ascites hepatomas to 1-beta-D-arabinofuranosylcytosine.

The biochemical basis for natural resistance to 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated in the intact cells of 4 rat ascites hepatomas, AH-66F, AH-60C, AH-109A, and AH-66, whose sensitivity to ara-C was different in that decreasing order. The initial rapid uptake of ara-C, mediated by the facilitated diffusion, was similar in all the cell lines tested but the subsequent slow uptake due to phosphorylation of ara-C was inversely correlated with their drug resistance. The capacity for drug phosphorylation was slightly higher in AH-66F and much lower in AH-60C, AH-109A, and AH-66 than in the host bone marrow. In contrast, mouse leukemia L-1210, one of the tumors sensitive to ara-C, phosphorylated the drug about 7 times faster than AH-66F and 4 times faster than the host bone marrow. More than 95% of phosphorylated ara-C was the triphosphate, the active form. Deamination of ara-C was not observed in any tumor or bone marrow. It is concluded that the low capacity for nucleotide formation is related to the natural resistance of rat ascites hepatomas to ara-C.

Animals↗
PubMed1976

Cell population size dependency of therapeutic effect of divided dosage of 1-beta-D-arabinofuranosylcytosine.

A total dose of 960 mg/kg body weight of 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside) was given intraperitoneally to rats bearing Yoshida sarcoma, in a single or divided doses. Single-dose therapy gave an increased life span of about 1 day irrespective of cell population size in accord with the concept of constant percentage cell kill. Tumor cell reduction was estimated to be about 70%. Divded-dose therapy, however, brought about increased life span which was reciprocally proportional to the logarithm of population size. Estimated cell reduction was 87% when population size was 10(8) cells and 99.95% at 10(4) cells.

Animals↗
PubMed1976

Beta-glucuronidase activity of Yoshida ascites hepatomas of different drug-sensitivity and its change after treatment of host rats with various anticancer agents.

Change in beta-glucuronidase activity of six Yoshida ascites hepatomas was examined after treatment of host rats with one of 12 anticancer agents. The hepatomas, AH-66F, AH-130, AH-109A, AH-60C, and AH-44, in decreasing order showed more or less distinct increase in beta-glucuronidase activity after treatment of the rats with Nitromin, Endoxan, 864-T, Carbazilquinone, Mitomycin-C, Toyomycin, Daunomycin, Neocarzinostatin, vincristine sulfate, 5-fluorouracil, or cytosine arabinoside only when the cytological effect was positive. Moreover, degree of the increase was generally correlated with that of cytological effect. Bleomycin was ineffective either enzymically or cytologically. AH-66 was insensitive to any of the agents tested in increasing beta-glucuronidase activity and showed only a very slight cytological response to some of the agents. Acid deoxyribonuclease behaved like beta-glucuronidase but to a lesser extent. The above order of drug sensitivity of the hepatomas was not in parallel with that of normal beta-glucuronidase level, which also did not correlate with the life span of host rats.

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